The major histocompatibility complex (MHC) includes genes which determine acceptance of allografts, genes which regulate interactions between immunocompetent cells, genes which control the synthesis of several complement components, Ir genes which regulate the ability to mount specific thymus dependent immune responses, and genes which encode two sets of cell plasma membrane glycoproteins which act as histocompatibility antigens. The two sets encoded within the guinea pig MHC, the GPLA complex, are the classical histocompatibility antigens, the GPLA-B and GPLA-S antigens and the Ia antigens. The research proposed will utilize a chemical approach to explore antigenic determinants, relationships between cell surface molecules, and relationships between Ia antigens and Ir gene products. Antigens will be internally labeled with 3H-leucine or 3H-fucose, solubilized by the non-ionic detergent NP-40, purified by lentil lectin affinity chromatography, isolated by immunoprecipitation, and examined by gel electrophoresis. By testing new alloantisera and using sequential immunoprecipitation techniques, the GPLA complex will be further defined. The protein or carbohydrate nature of the antigenic determinant will be explored using pronase and glycosidase digestion. Each chain of the two chain Ia molecule will be examined for the Ia determinant and to determine if either chain has the necessary microheterogeneity to make it an antigen receptor. Cell surface antigen organization will be explored by a membrane protein nearest neighbor analysis by cross-linking proteins prior to cell solubilization. Chemical differences in Ia molecules derived from different lymphoid populations will be sought. Partial amino acid sequencing of the GPLA-B antigen is proposed. The presence of immunglobin idiotypes in guinea pig T cell receptors and the presence of VH allotypes in rabbit T cell receptors will be tested.